Rucaparib shows encouraging responses in advanced pancreatic cancer
Oral rucaparib as maintenance treatment showed encouraging clinical responses in patients with advanced BRCA1-, BRCA2-, or PALB2-mutated pancreatic cancer, according to an interim analysis presented at AACR 2019.
“In this [unplanned] interim analysis, we are finding that patients with platinum-sensitive pancreatic cancer appear to benefit from treatment with single-agent rucaparib,” said study lead author Assistant Professor Kim Reiss Binder from the Department of Medicine, Division of Hematology Oncology at the University of Pennsylvania in Philadelphia, Pennsylvania, US.
This single-arm, phase II trial evaluated 24 patients with advanced pancreatic cancer who had received prior platinum-based chemotherapy for >4 months. All patients were given 600 mg rucaparib twice daily and continued treatment until disease progression or intolerable toxicity. [AACR 2019, abstract CT234]
At the time of analysis, only 19 patients (median age 61 years, 84.2 percent female) were evaluable for progression-free survival (PFS). Of these, three and 13 patients had germline BRCA1 and BRCA2 mutations, respectively, one had a somatic BRCA2 mutation, and two had PALB2 mutations.
Patients who received rucaparib had a median PFS of 9.1 months.
The overall response rate was 36.8 percent, with six patients having a partial response (PR) and one patient having a complete response (CR). Patients treated with rucaparib also showed a disease control rate (defined as the total rate of PR, CR, and stable disease) of 89.5 percent at ≥8 weeks.
“Several patients had complete or partial responses with rucaparib treatment, suggesting that this therapy has the potential not only to maintain the disease, but also to shrink the tumours in some instances,” Reiss Binder noted.
The most common treatment-related adverse event reported was grade 1 and 2 nausea (41.6 percent and 4.2 percent, respectively), with only one patient requiring a dose reduction, followed by grade 1 dysgeusia (33.3 percent) and fatigue (25 percent).
“While this subgroup of pancreatic cancer patients responds well to platinum-based chemotherapy, prolonged treatment leads to cumulative toxicity, so this approach often becomes unsustainable. We wanted to investigate more tolerable maintenance options, as there are no approved treatments in this setting,” Reiss Binder said.
“Although this is very preliminary data, the fact that we're seeing sustained clinical responses [with minimal toxicity] in some of these patients is very exciting,” noted Reiss Binder. “Other than the recent tissue-agnostic approval of pembrolizumab for patients with microsatellite instability-high tumours, there really is no other targeted therapy that has shown promise for patients with pancreatic cancer.”
“Our results [also] highlight the importance of germline and somatic testing in pancreatic cancer patients,” said Reiss Binder. “The presence of certain mutations can guide treatment strategies, and patients should know to ask their oncologist about getting tested.”
As this was an unplanned interim analysis of an ongoing phase II study, further validation of the results is warranted, she said.